A Troublesome Inheritance was published in 2014 by Penguin Books. Cover image via Google Books.

Last week at Nothing In Biology Makes Sense, I began critiquing Nick Wade’s latest book, A Troublesome Inheritance. The book has produced a firestorm of criticism, largely because it argues that evolution has produced significant cultural and behavior differences between races.

Wade makes many sweeping claims, among them: that natural selection has made the English inherently fiscally prudent and more likely to defer gratification by saving for tomorrow, that events early in the history of Judaism caused the Jews to evolve features predisposing them to careers in banking, and that genetic variation in certain neurochemicals has made Africans inherently more violent.

Wade hangs these seemingly bizarre conclusions on the mantle of modern population genetics, which he claims confirms the existence of ‘three primary races,’ that have evolved real and significant cultural differences between them. By heavily referencing the scientific literature, Wade manages, as Mike Eisen put it, to “give the ideas that he presents… the authority of science… What separates Wade’s theories – in his own mind – from those of a garden variety racist is that they are undergirded by genetics.”

Unfortunately for Wade, the current scientific literature actually contradicts much of what he reads into it. Last week, I looked at Wade’s assertion that modern genetics identifies “3 primary races.” It turns out that if we allow the data to tell us how many discrete populations exist within humans we would find at least 14 (Tishkoff et al. 2009). In addition, recent work shows that the genetic differentiation between ethnic groups within races is much greater than the genetic differentiation between races (Moreno-Estrada et al. 2014)[1]. This week, I will look at Wade’s arguments that natural selection has produced differences in behavior between races.

In trying to make the case that differences between human societies and cultures are the result of different evolutionary pressures and resulting differences in genetic make-up, Wade relies heavily on studies of the monoamine oxidase A (MAO-A) gene. MAO-A is an enzyme that degrades certain neurotransmitters – the signaling molecules that carry messages between neurons. A number of studies using both observational and experimental approaches suggest that low levels of MAO-A activity are associated with impulsivity, violence, and anti-social behavior (Pavlov et al. 2012) in both humans and in mice.

A synapse – the junction between two nerve cells. Neurotransmitters are released by the presynaptic nerve cell into the space between the neurons. These then bind to receptors on the post-synaptic nerve, propagating a neurochemical signal in the next nerve cell. Afterwards, the neurotransmitters may be reabsorbed into the presynaptic cell and degraded by enzymes like Monoamine Oxidase A. Image is by Nrets, via Wikimedia Commons.

In reviewing this literature Wade asks, “If individuals can differ in the genetic structure of their MAO-A gene and its controls is the same also true of races and ethnicities?” He then gives an immediate, confident reply to his own rhetorical question: “The answer is yes.” Wade then goes on to mine the genetic literature, uncovering evidence that (he claims) shows that natural selection has favored different variants of MAO-A in different races. He even purports to find evidence that African American men have low levels of MAO-A activity, perhaps producing an inherent genetic predisposition to violence. At this point, Wade seems to lose the courage of his convictions cautioning that,

A finding like this has to be interpreted with care… even if African Americans are more likely to carry the violence-linked allele of MAO-A … Caucasians may carry the aggressive allele of other genes.

Indeed, such a finding would need to be interpreted with care, but apparently that care does not extend to fact-checking, as almost none of what Wade says about the research on MAO-A is supported by the literature he cites. Genetic variation associated with aggressive and anti-social behavior is found in the promoter region of MAO-A – the upstream control that help to determine when the MAO-A gene is turned on, and how much of MAO-A enzyme is ultimately produced. However, the study that Wade cites to substantiate his claim that natural selection has produced differences in MAO-A between populations (Gilad et al. 2002) did not examine variation in the promoter region. Instead, the Gilad paper focused on variation within the gene itself. So, if there had been selection acting on variation in MAO-A’s promotor, the Gilad study might not have found it.

A promoter is a section of DNA that is involved in the expression of a gene, by allowing the enzyme RNA Polymerase to bind to DNA, and subsequently transcribe DNA into RNA. Promoters can also play an important role in regulating the expression of the gene, that is, determining when the gene is turned on, in which cells, and how strongly it is expressed. Different genetic variants in the promoter region of the MAO-A gene effect how much of the MAO-A gene is produced. Image is by Darryl Leja of the National Human Genome Center.

Furthermore, the evidence that Gilad and colleagues found indicating natural selection in MAO-A is very likely to have been a ‘false positive.’ Briefly, the Gilad study used measures of genetic variation in the MAO-A gene as a way to identify the fingerprint of natural selection. As a beneficial mutation spreads through a population, it tends to carry other genes located nearby on the chromosome along with it. The result is that regions of the genome affected by natural selection tend to show relatively little genetic variation, and where there is genetic variation, these variants tend to be rare[2]. However, this same pattern can also be produced by demographic changes – such as the rapid expansion of the human population in the last ten thousand years. As a result, it is often difficult to determine whether the patterns of variation found in a gene are the product of natural selection or demographic effects. In fact, one of the co-authors of the Gilad study, the eminent population geneticist Molly Przeworski, later evaluated the statistical tools used to identify selection acting on MAO-A, and found that their approach is particularly prone to producing false-positives (that is, the method they used often finds evidence of natural selection in genes that did not experience it; Przeworski 2002).

To distinguish the effects of demography from the effects of selection, comparisons with other genes are needed. Subsequent work by Rasmus Nielsen and Scott Williamson completed exactly these comparisons, seeking to distinguish the effects of natural selection acting on the human genome from the effects of population growth (Nielsen et al. 2005; Williamson et al. 2007). By correcting for the overall low levels of genetic variation and the excess of rare genetic variants caused by population growth, Nielsen and Williamson’s studies were able to identify many regions in the genome that appear to have experienced recent natural selection, but MAO-A is not one of them. Indeed, the Nielsen study specifically tested for selection acting on the MAO-A gene (among thousands of others) but found no evidence for positive selection acting on this gene[3].

Finally, work by Voight and Pritchard, which Wade discusses prominently in his chapter on human genetics, scanned the entire human genome for evidence that natural selection has produced differences between ethnicities[4], and although they identified hundreds of regions of the human genome that have diverged through natural selection, the region containing MAO-A was not one of them[5] (Voight et al. 2006).

Although some studies have found genetic variants in the MAO-A promoter region that are more common in some ethnic groups than in others (Sabol et al. 1998; Widom & Brzustowicz 2006; Reti et al. 2011) it is likely that these genetic variants are not –on their own– associated with violent or impulsive behavior (Caspi et al. 2002; Widom & Brzustowicz 2006). Instead, genetic variation in the MAO-A promoter seems to make some children less able to recover from abuse and childhood trauma, and therefore more likely to act out later in life (Caspi et al. 2002; Widom & Brzustowicz 2006). Simply carrying the ‘low expression’ allele in the MAO-A promoter does not have any effect at all on impulsivity or aggression. It therefore seems highly unlikely that variation in the MAO-A promoter has produced a greater inclination towards violence in Africans, as Wade suggests. Indeed, genetic variants associated with lower resilience to trauma are most common in Asian populations, not African ones (Sabol et al. 1998)[6].

So, as yet, no genes have yet been identified that – on their own – explain a tendency for violent behavior (at least none that I am aware of). If such genes exist, it is theoretically possible that natural selection might cause them to become common in some populations but not others. For the moment, however, we have no evidence that natural selection has acted on MAO-A.

Next week, I will look at whether natural selection has produced significant differences between races overall.

Acknowledgements: Thanks are due to Molly Przeworski for discussion of her 2002 paper, and to Emily Drew, Malia Santos, Furey Stirrat, and Jeremy Yoder for comments on earlier drafts of this post.

References

Caspi A. (2002). Role of genotype in the cycle of violence in maltreated children, Science, 297 (5582) 851-854. DOI: 10.1126/science.1072290

[1] In a future post I will discuss the difference between genetic variation ‘within races’ versus genetic variation ‘between races’ in greater detail.

[2] For the detail-oriented – I am referring here to something called the site frequency spectrum, a count of how many copies of a gene, drawn from a particular sample of a population, carry a mutation at a particular site. My description above pertains specifically to what we expect to see in the site frequency spectrum for a gene following a selective sweep – when a beneficial mutation rapidly sweeps through the population. The initial sweep eliminates genetic variation in regions of the genome adjoining the selected site. Mutations that arise in these adjoining regions following the sweep tend to be present in one or a few gene copies, leading to an excess of unique and low-frequency polymorphisms. Other forms of natural selection, such as purifying selection, which acts to eliminate harmful mutation, or balancing selection, that maintains two different genetic variants in the population, will produce different patterns.

[3] Again, for the detail oriented, Nielsen’s study used a likelihood ratio test to evaluate whether the number of mutations that changed the encoded amino acid (non-synonymous mutations, dN) was greater than the number of mutations that did not (synonymous mutations, dS). Typically a dN/dS ratio of greater than 1 is seen as evidence of positive selection. For the MAO-A gene, Nielsen and colleagues found no evidence whatsoever that dN/dS was greater than 1. That is, their test showed that evidence for positive selection acting on this gene were as far from statistically significant as it is possible to get (p=1). Williamson’s study looked specifically at the site frequency spectrum, and thus is more comparable to the previous Gilad study, and also did not identify MAO-A as a region under selection.

[4] Wade reports, incorrectly, that this paper identified differences between races, but the sampling scheme in the study does not allow us to determine whether the differences identified are between the population groupings that Wade identifies as separate races, or between smaller groupings within them.

[5] You don’t have to take my word for it; Pritchard’s team created a handy web-browser where you can search for specific genes or specific sections of a chromosome and determine whether these show evidence of positive selection. You can view it here: http://haplotter.uchicago.edu/.

[6] Note that Sabol study did not consider differences between populations in the frequencies of the ‘2-repeat’ alleles that Wade references, which appears to be extremely rare with an average frequency of 2% across the populations that have been studied (Widom & Brzustowicz 2006). To my knowledge, the frequency of the 2-repeat allele across populations has not been extensively measured; studies that have looked at its incidence appear to have focused on specific cohorts in the US as part of epidemiological studies.